Impact of 2018 EU Risk Minimisation Measures and Revised Pregnancy Prevention Programme on Utilisation and Prescribing Trends of Medicinal Products Containing Valproate: An Interrupted Time Series Study

• DOI: 10.1007/s40264-023-01314-3
• Publication Date: 2023-06-09T13:01:53Z
• Authors: Shahab Abtahi; Romin Pajouheshnia; Carlos E. Durán; Judit Riera-Arnau; Magdalena Gamba; Ema Alsina; Vjola Hoxhaj; Morten Andersen; Claudia Bartolini; Sarah Brøgger Kri...; Jeremy Brown; Christine Erikstr...; Patricia Garcia-Poza; Helga Gardarsdottir; Rosa Gini; Anna Girardi; Emily Holthuis; Consuelo Huerta; Luisa Ibánez; Giorgio Limoncella; Mar Martín-Pérez; Olga Paoletti; Giuseppe Roberto; Patrick Souverein; Karin M. A. Swart; Kevin Wing; Miriam Sturkenboom; Olaf Klungel
• Keywords: Minimisation (clinical trials); Pharmacoepidemiology

Due to established teratogenicity of valproates, the EU risk minimisation measures (RMMs) with a pregnancy prevention programme (PPP) for valproate were updated in March 2018.To investigate effectiveness 2018 RMMs on utilisation five European countries/regions.A multi-database, times series study females childbearing potential (12-55 years) was conducted using electronic medical records from countries/regions (01.01.2010-31.12.2020): Denmark, Tuscany (Italy), Spain, Netherlands, and UK. Clinical demographic information each database transformed ConcePTION Common Data Model, quality checks distributed analysis performed common scripts. Incident prevalent use valproate, proportion discontinuers switchers alternative medicine, frequency contraception coverage during use, occurrence pregnancies exposure estimated per month. Interrupted time analyses estimate level or trend change outcome measures.We included 69,533 users 9,699,371 participating centres. A significant decline valproates observed Tuscany, Italy (mean difference post-intervention -7.7%), Spain (-11.3%), UK (-5.9%) non-significant Netherlands (-3.3%), but no incident after compared period before. The monthly compliant prescriptions/dispensings contraceptive low (<25%), an increase only 12%). There switching rates medicine intervention any countries/regions. We substantial number concurrent exposure, declining rate (0.70 1000 pre- 0.27 post-intervention), (0.48 0.13), (0.34 0.00), increasing (1.13 5.07).There small impact studied warrants careful monitoring implementation existing PPP clinical practice Europe, see if there is need additional future.